Background Diabetes mellitus increases the excretion of urinary glucose from the renal glomeruli due to elevated blood glucose levels. In the renal tubules, SGLT2 is expressed and reabsorbs the excreted urinary glucose. In the pathogenesis of diabetes mellitus, glucose reabsorption by SGLT2 is increased, and SGLT2 inhibitors improve hyperglycaemia by inhibiting this reabsorption. When urinary glucose excretion is enhanced, glucose supply to skeletal muscle may be insufficient and muscle protein catabolism may be accelerated. On the other hand, SGLT2 inhibitors not only ameliorate hyperglycaemia but also improve fatty acid metabolism in muscle, which may prevent muscle atrophy. Methods Eight-week-old male db/m mice or db/db mice were fed a standard diet with or without the SGLT2i luseogliflozin (0.01% w/w in chow) for 8 weeks. Mice were sacrificed at 16 weeks of age, and skeletal muscle and serum lipidomes, as well as skeletal muscle transcriptome, were analysed. Results Administration of SGLT2i led to not only decreased visceral fat accumulation (P = 0.004) but also increased soleus muscle weight (P = 0.010) and grip strength (P = 0.0001). The levels of saturated fatty acids, especially palmitic acid, decreased in both muscles (P = 0.017) and sera (P = 0.041) upon administration of SGLT2i, while the content of monosaturated fatty acids, especially oleic acid, increased in both muscle (P < 0.0001) and sera (P = 0.009). Finally, the accumulation of transcripts associated with fatty acid metabolism, such as Scd1, Fasn, and Elovl6, and of muscle atrophy-associated transcripts, such as Foxo1, Mstn, Trim63, and Fbxo32, decreased following SGLT2i administration. Conclusions Intramuscular fatty acid metabolism and gene expression were influenced by the extracellular lipidome, which was modified by SGLT2i. Hence, secondary effects, other than the hypoglycaemic effects of SGLT2i, might lead to the alleviation of sarcopenia.
The progression of nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. NAFLD patients generally do not respond to treatment with testosterone alone. In animal studies, treatment with testosterone and estrogen reduced the ratios of ILC2:CD45 and ILC3:CD45 and increased M2 macrophages in liver. Our study suggests, based on our immunological data, that a combination of estrogen and testosterone may be clinically relevant for the treatment of NAFLD in patients with male menopause.
Background and Aims: Visceral adiposity index (VAI), calculated with body mass index, high density lipoprotein-cholesterol, triglycerides and waist circumference, has been proposed as a marker of visceral fat accumulation and dysfunction in adipose tissue. Methods: The impact of VAI on incident chronic kidney disease (CKD) in a historical cohort study of 15,159 (8,260 men and 6,899 women) participants was investigated. CKD was defined when estimated glomerular filtration rate was < 60 mL/min/1.73 m 2 or proteinuria (positive: ≥1+). We divided the participants into 2 groups according to sex and into quartiles according to VAI (Q1-4). We performed Cox proportional hazard models, adjusting for age, smoking status, exercise, alcohol consumption, systolic blood pressure, hemoglobin A1c, uric acid, and creatinine. Results: During the median 3.3-year follow-up for men and 3.2-year follow-up for women, 1,078 participants (629 men and 449 women) developed CKD. The 4,000 days cumulative incidence rate of CKD for men and women were 3.7 and 3.9% in Q1, 5.2 and 5.9% in Q2, 6.5 and 7.0% in Q3, and 8.4 and 9.3% in Q4 respectively. Compared to Q1, the hazard ratios of incident CKD in Q2, Q3 and Q4 for men and women were 1.23 (95% CI 0.91-1.66, p = 0.184) and 1.30 (0.87-1.96, p = 0.203), 1.42 (1.06-1.90, p = 0.018) and 1.38 (0.94-2.05, p = 0.105), and 1.51 (1.12-2.02, p = 0.006) and 1.65 (1.12-2.46, p = 0.013) respectively. Additionally, the area under the curve of VAI for incidence of CKD was superior to that of VAI in men (0.595 vs. 0.552, p < 0.001) and equal to in women (0.597 vs. 0.591, p = 0.708). Conclusions: The VAI can be a predictor of incident CKD.blood after an overnight fast. We used the Japanese Society of Nephrology equation for calculating each patient's estimated GFR (eGFR): eGFR (mL/min/1.73 m 2 ) = 194 × serum creatinine -1.094 × age -0.287 (× 0.739 for women) [14]. Spot morning urine sample was measured.
In recent years, sarcopenic obesity has been considered central pathological factors in diabetes. This study aimed to compare the effect of luseogliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i), on sarcopenic obesity in comparison to that of a low-carbohydrate diet (LCD). Twenty-week-old male db/db mice were fed a normal diet (Ctrl), LCD, and normal diet with 0.01% w/w luseogliflozin (SGLT2i) for eight weeks. Skeletal muscle mass and grip strength decreased in the LCD group mice compared to those in the control group, while they increased in the SGLT2i group mice. The amino acid content in the liver, skeletal muscle, and serum were lower in the LCD group than those in the Ctrl group but increased in the SGLT2i group mice. Short-chain fatty acids in rectal feces were lower in the LCD group mice than those in the Ctrl group, whereas they were higher in the SGLT2i group mice. The abundance of Gammaproteobacteria, Enterobacteriaceae, Escherichia, Enterobacterales, and Bacteroides caccae species increased in the LCD group compared to the other two groups, whereas the abundance of Syntrophothermus lipocalidus, Syntrophomonadaceae family, Parabacteroidesdistasonis distasonis, and the genus Anaerotignum increased in the SGLT2i group. Luseogliflozin could prevent sarcopenic obesity by improving amino acid metabolism.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.